Green adherent spectrophotometric determination of molnupiravir based on computational calculations; application to a recently FDA-approved pharmaceutical dosage form.

Molnupiravir is an oral antiviral drug developed to provide significant benefit in reducing hospitalizations or deaths in mild COVID-19. Integrated green computational spectrophotometric method was developed for the determination of molnupiravir. Theoretical calculations were performed to predict the best coupling agent for efficient diazo coupling of molnupiravir. The binding energy between molnupiravir and various phenolic coupling agents, α-naphthol, ß-naphthol, 8-hydroxyquinoline, resorcinol, and phloroglucinol, was measured using Gaussian 03 software based on the density functional theory method and the basis set B3LYP/6-31G(d). The results showed that the interaction between molnupiravir and 8-hydroxyquinoline was higher than that of other phenolic coupling agents. The method described was based on the formation of a red colored chromogen by the diazo coupling of molnupiravir with sodium nitrite in acidic medium to form a diazonium ion coupled with 8-hydroxyquinoline. The absorption spectra showed maximum sharp peaks at 515 nm. The reaction conditions were optimized. Beer's law was followed over the concentration range of 1-12 µg/ml molnupiravir. Job's continuous variation method was developed and the stoichiometric ratio of molnupiravir to 8-hydroxyquinoline was determined to be 1:1. The described method was successfully applied to the determination of molnupiravir in pure form and in pharmaceutical dosage form. The results showed that the proposed method has minimal environmental impact compared to previous HPLC method.

Different spectrophotometric methods for simultaneous determination of lesinurad and allopurinol in the new FDA approved pharmaceutical preparation; additional greenness evaluation.

Lesinurad and allopurinol have been formulated in a combined dosage form providing a new challenge for the treatment of gout attacks. Two mathematical based spectrophotometric methods, area under the curve, and artificial neural networks have been developed for simultaneous determination of lesinurad and allopurinol in pure form and in combined pharmaceutical dosage form. Area under the curve has been utilized to resolve the spectral overlap between lesinurad and allopurinol. Values of area under the curve and area absorptivity were measured at two selected wavelength ranges of 242-250 nm and 255-265 nm. Two mathematically constructed equations have been used to determine the concentrations of the drugs under the study. Advanced chemometry based model, artificial neural network, has been developed utilizing the UV spectral data of lesinurad and allopurinol through various defined steps. A five-level, two-factor experimental design was used to construct 25 mixtures. Thirteen mixtures were used to set up the calibration model and 12 mixtures were used to construct a validation set. The artificial neural network model was optimized to enable precise spectrophotometric determination of the drugs under the study. The described mathematically bases spectrophotometric methods have been successfully applied to the determination of lesinurad and allopurinol in the new combined, Duzallo® tablets. Furthermore, the greenness of the described methods was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The proposed methods showed more adherence to the greenness characters in comparison to the previously reported HPLC method.